concanavalin-a and Disseminated-Intravascular-Coagulation

Tumor cells interact with the hemostatic system in various ways and may thus influence malignant growth and spread. MC28 fibrosarcoma cells possess a potent procoagulant activity (PCA) and form lung tumors following intravenous injection. The aim of this work was to study the relationship between PCA, intravascular coagulation and lung seeding in the MC28 model. MC28 cells were injected into control, warfarinized and heparinized hooded Lister rats. Coagulation changes were monitored by thromboelastography (TEG) and Sonoclot analysis (SA), lung fibrin formation by light and electron microscopy, tumor seeding by macroscopic counting and tumor cell and platelet deposition in the lungs by radiolabelling. PCA was measured by chromogenic assay. MC28 PCA was characterized as a tissue factor-factor VIIa complex that probably arose during cell culture or disaggregation of solid tumors. Injection of tumor cells caused marked coagulopathy and was rapidly (within 30 min) followed by fibrin deposition in the lungs and accumulation of radiolabelled platelets. Heparin and warfarin significantly reduced lung seeding (p < 0.001) and reduced retention of radiolabelled tumor cells in the pulmonary circulation (p < 0.01). Inhibition of cellular PCA by prior treatment with concanavalin A markedly reduced intravascular coagulation and lung seeding. We conclude that MC28 cells cause intravascular coagulation as a direct result of their procoagulant activity. The data suggest that tumor cells form complexes with platelets and fibrin which are retained in the lungs long enough for extravasation and seeding to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Cell Adhesion; Concanavalin A; Culture Media, Serum-Free; Cysteine Endopeptidases; Disseminated Intravascular Coagulation; Fibrin; Fibrosarcoma; Heparin; Injections, Intravenous; Lung; Lung Neoplasms; Macrophage Activation; Male; Neoplasm Proteins; Neoplasm Transplantation; Neoplastic Cells, Circulating; Pulmonary Circulation; Rats; T-Lymphocytes; Tumor Cells, Cultured; Warfarin

Precipitation pattern of factor VIII related antigen (VIIIR:AG) with concanavalin A (Con A), a glycoprotein binding lectin, was investigated in normal subjects and patients with a variant of von Willebrand's disease (VWD) and disseminated intravascular coagulation (DIC). Decreased precipitation with Con A was demonstrated in patients with a variant of VWD in which VIIIR:AG showed an increase in electrophoretic mobility on crossed immunoelectrophoresis (CIE). Similar findings were obtained in patients with DIC which revealed normal electrophoretic mobility of VIIIR:AG. This procedure was assumed to be useful for the detection of a qualitative abnormality of the factor VIII protein.

Topics: Antigens; Concanavalin A; Disseminated Intravascular Coagulation; Factor VIII; Humans; Precipitin Tests; von Willebrand Diseases